RAGs’ eye view of the immunoglobulin heavy chain gene locus

The immunoglobulin heavy chain (IgH) gene locus is activated at a precise stage of B lymphocyte development to undergo gene rearrangements that assemble the functional gene. In this review we summarize our current understanding of the chromatin state of the IgH as it appears just prior to the initiation of V(D)J recombination, and the implications of this structure for regulation of recombination. We also examine the role of the intron enhancer, Eμ, in establishing the pre-rearrangement chromatin structure. The emerging picture shows that the IgH locus consists of independently regulated domains, each of which requires multiple levels of epigenetic changes to reach the fully activated state.